A. Abstract There are approximately 240,000 U.S. taxi/limousine drivers in the U.S.(1). New York City (NYC) is home to 42,000 taxi drivers, 84% of whom are immigrants (2). NYC taxi drivers work long hours (10-12 h/d shifts, ~6d/wk), often in heavy traffic (2). Exposure to high levels of respirable particulate matter (PM) is closely linked to increased hospital admissions, lung cancer risk and mortality, and respiratory and cardiopulmonary mortality (3-9). Two studies have demonstrated high lung cancer prevalence among professional drivers, after adjusting for smoking, suggesting an association with PM exposure (10, 11). In a reanalysis ofthe Harvard Six Cities Study, each 10 pg/m^ increase in PM2.5 exposure was associated with an adjusted increased risk of all-cause mortality of 14% (95% Cl: 7, 22), and with a 37% (95% Cl: 7, 75) increase in lung cancer mortality (12). A 26- year prospective study found that each 10 pg/m^ increase in PM2.5 (PM <2.5 pm) exposure is associated with a 15-27% increase in lung cancer mortality among never-smokers (3). Taxi Particulate matter Study (TIPS) is a community-engaged T1-T4 translational research study for at-risk taxi drivers in NYC. TIPS will address the following key research questions: 1) the extent to which excess PM exposure is associated with adverse changes in physiologic and biochemical markers, by comparing drivers with a driver nominated non-taxi-driver peer comparison group; 2) the effect of an In-taxi HEPA filtration intervention on decreasing PM exposure and associated biomarker levels among taxi drivers randomized to the HEPA intervention in comparison with taxi drivers randomized to a control group. Participating taxi drivers will be randomized with a 1:1 ratio into either the control condition or the HEPA filter intervention condition. A third, driver-nominated matched peer reference group will serve as non-taxi-driver controls. Aim 1 - To determine in-vehicle excess PM exposure, including size distribution, mass concentration, and chemical composition among taxi drivers (measured during work shifts and at home) compared to a matched non-driver peer reference group; and to assess whether excess PM exposure is associated with changes in intermediate physiologic and biochemical markers of lung cancer. Portable monitors will be used to measure PM, and a mini-aethalometer to measure black carbon, a marker of diesel exhaust, and a known carcinogen (13). An organic compound screening method will also be used to identify organic compounds in atmospheric aerosols with gas chromatography/mass spectrometry (GC/MS); metals will also be analyzed. Physiologic and biochemical markers will include pro/anti-inflammatory cytokines, exhaled nitrite/nitrate (indicators of oxidative stress), and epigenetic changes associated with cancer and/or inflammation. There are data showing that increased levels of inflammatory cytokines and exhaled nitrite/nitrate in exhaled breath condensate and bronchoalveolar lavage fluid are associated with lung cancer (14-16). Epigenetic methylation of specific genes has been associated with lung cancer, and can precede clinical diagnosis by up to three years (17, 18). Hypothesis 1 - Taxi drivers in NYC are exposed to elevated PM levels in their vehicles during work shifts, and have associated elevated cytokine levels, increased exhaled nitrite/nitrate, and methylation of specific genes, all of which are likely to be associated with and/or predictive of lung cancer risk (compared to a matched peer reference group and to themselves before/after work). Aim 2 - To use a randomized controlled design to assess if a targeted intervention, installation of a portable car high-efficiency particulate air (HEPA) filter (to remove PM and volatile organic compounds), results in a reduction of in-vehicle PM exposure and associated physiologic and biochemical markers among taxi drivers. Hypothesis 2 - Installation of a small, portable, low-cost (<$200), easy to use, car HEPA filter will result in a reduction of in-vehicle PM exposure and associated physiologic and biochemical markers of risk among drivers. Aim 3 - To disseminate results of Aims 1 and 2 at the individual and systems level through community engaged risk education programs. A risk education program will be developed on occupational risks, exposure to PM, associated health risks, and methods to reduce these risks. Study results will be disseminated at airport holding lots, through the One NYC One Nation initiative, through the New York Taxi Workers' Alliance, and through academic publications and presentations. Hypothesis 3 - Data about PM risks, and risk-reducing interventions, can be effectively disseminated through community-engaged risk education programs.